Polymer scaffolds have been employed in order to provide a base structure for macromolecular conjugates. Commercially available poly(ethylene glycol) scaffolds suffer from a variety of problems including the lack of attachment sites and polydispersity. For example, the following two different PEG carrier conjugates had previously been used for linking multiple copies of two different effector substances. In one publication, Zhang et al., “Multiple peptide conjugates for binding β-amyloid plaques of Alzheimer's disease,” Bioconjugate Chemistry 14, 86-92 (2003), 6 copies of the D-amino acid peptide, phe-phe-val-leu-lys-cys (SEQ ID NO: 6) and 2 copies of the reporter group, biotin, were linked to an 8-ann branched PEG (Nektar Therapeutics, Ala, USA). In another publication, Pooyan et al., “Conjugates bearing multiple formyl-methionyl peptides display enhanced binding to but not activation of phagocytic cells,” Bioconjugate Chemistry 13, 216-223 (2002), varying amounts of the peptide, N-formyl-Met-Leu-Phe (f-MLF), were linked to either an 8-arm branched PEG to form about 4 copies of peptide and 4 copies of the reporter group, digoxigenin, were linked to the 8-arm PEG. In order to arrive at this ratio of effectors, one of them must be attached first and then quantitated. The second effector is then added and either quantitated or assumed to fill the sites not occupied by the first effector. Furthermore, there should be a distribution of appended effectors. That is, there might be 4 copies of peptide and 4 copies of digoxigenin on a large portion of carrier PEGs, but there will also be some carriers having 3 and 5 or 2 and 6 copies due to the randomness of the reaction sites on the carrier. This is an example of polydispersity, since the f-MLF peptide, N-formyl-Met-Leu-Phe and the digoxigenin are present in different ratios on individual carrier molecules.
There exists a need for a means by which monodispersed conjugates of two substances or a polymer scaffold can be prepared in high yields to eliminate the need to isolate a desired conjugate fraction.